The general purposes of this research are to understand the physical and chemical bases of the properties and function of proteins, with particular reference to the fibrous protein, collagen. The aims of this program are to elucidate the way in which the crosslinks of collagen participate in its biologic role of imparting form, strength and support to the tissues. The experimental approach includes labelling of the crosslinks and their precursors in collagen by specific chemical means followed by their isolation and the elucidation of their structure. The location of these compounds is then established by isolating portions of the protein which contain them. As the structural information becomes well delineated, its relationship to the biology of maturation, to phylogenetic variations, and possible alterations in the hereditary and acquired diseases of connective tissue will be explored. By this approach, a correlation of the biologic functions and chemistry of collagen should be possible, providing insight into the activities and properties of an important natural polymer.